A data accuracy evaluation strategy to improve the representation of potential pesticide use areas for endangered species assessments.

The use of "best available data" is a fundamental requirement for all scientific forms of analysis. This paper discusses ways to improve the accuracy of data used to evaluate the potential impacts of pesticides on species that are listed as threatened or endangered under the Endangered Species Act (ESA) by ensuring the best available spatial data representing pesticide use sites are applied correctly. A decision matrix is presented that uses accuracy information from metadata contained in the US Department of Agriculture's (USDA's) Cropland Data Layer (CDL) and the Census of Agriculture (CoA) to improve how labeled pesticide use sites are spatially delineated. We suggest recommendations for the current pesticide evaluation process used by the US Environmental Protection Agency (USEPA) and subsequently by the US Fish and Wildlife Services and National Marine Fisheries Service (collectively known as the Services) in Section 7 consultation activities. The decision matrix is applied to each cultivated land layer in the USDA's CDL with recommendations for how best to use each layer in the evaluation process. Application of this decision matrix will lead to improved representation of labeled uses and more accurate overlap calculations used in the assessment of potential impacts of pesticides on endangered species. Integr Environ Assess Manag 2022;18:1655-1666. © 2022 SETAC.

Ultrasound Detection of Human Botfly Myiasis of the Scalp: A Case Report.

Dermatobia hominis, also known as the human botfly, is an insect native to Central and South America that is known to parasitize both human and animal hosts through cutaneous infestation by its developing larvae. While human botfly myiasis has been commonly diagnosed through dermatologic findings, the presenting lesions and associated symptoms can be non-specific and often misconstrued as other more common cutaneous diagnoses. Here, we present a case of botfly myiasis of the scalp in which ultrasound was utilized to visualize the larvae and confirm the diagnosis prior to larval removal. In this report, we discuss our patient's presentation, ultrasound imaging, and clinical course/treatment in order to convey how ultrasound imaging, when available, is a valuable tool in establishing the diagnosis of human botfly myiasis.

Interleukin-6 Promotes Murine Estrogen Deficiency-Associated Cerebral Aneurysm Rupture.

BACKGROUND: Estrogen deficiency is associated with cerebral aneurysm rupture, but the precise mechanism is unknown. OBJECTIVE: To test the hypothesis that IL-6 is required for the increase in aneurysm rupture rate observed in estrogen-deficient mice. METHODS: We analyzed IL-6 expression in human cerebral aneurysms. We induced cerebral aneurysms in estrogen-deficient female C57BL/6 mice that had undergone 4-vinylcyclohexene diepoxide (VCD) treatment or bilateral ovariectomy (OVE). Mice were blindly randomized to selective IL-6 inhibition (IL-6 receptor [IL-6R] neutralizing antibody, n = 25) or control (isotype-matched IgG, n = 28). Murine cerebral arteries at the circle of Willis were assessed for aneurysm rupture and macrophage infiltration. RESULTS: IL-6 is expressed in human cerebral aneurysms, but not in control arteries. Serum IL-6 is elevated in ovariectomized female mice compared to sham control (14.3 ± 1.7 pg/mL vs 7.4 ± 1.5 pg/mL, P = .008). Selective IL-6R inhibition suppressed cerebral aneurysm rupture in estrogen-deficient mice compared with control (VCD: 31.6% vs 70.0%, P = .026; OVE: 28.6% vs 65.2%, P = .019). IL-6R inhibition had no effect on formation or rupture rate in wild-type mice. IL-6R neutralizing antibody significantly reduced macrophage infiltration at the circle of Willis (1.9 ± 0.2 vs 5.7 ± 0.6 cells/2500 µm2; n = 8 vs n = 15; P < .001). CONCLUSION: IL-6 is increased in the serum of estrogen-deficient mice and appears to play a role in promoting murine estrogen deficiency-associated cerebral aneurysm rupture via enhanced macrophage infiltration at the circle of Willis. Inhibition of IL-6 signaling via IL-6 receptor neutralizing antibody inhibits aneurysm rupture in estrogen-deficient mice. IL-6 receptor inhibition had no effect on aneurysm formation or rupture in wild-type animals.

Integrating Individual Student Advising into Financial Education to Optimize Financial Literacy in Veterinary Students.

The debt-to-income ratio (DIR) of Doctor of Veterinary Medicine (DVM) students has exceeded the recommended 1.4 and it is predicted that the DIR will approach 2.18 by 2026. The associated stressors negatively impact professional satisfaction and well-being. In conventional approaches to financial education, content is delivered to groups of students as part of the curriculum, but with little opportunity for application. Research in medical and financial education suggests that convenient timing, relevant subject matter and individualization are key characteristics of a successful program that promotes retention and application of knowledge. In this article, we describe an integrative approach to financial education developed by the Colorado State University (CSU) Financial Education Specialist (FES). The FES position requires that the individual be qualified to provide one-on-one financial advising to DVM students as well as develop targeted curricular interventions and optional workshops. Data from student and alumni surveys suggest that this integrative approach to financial education both improves knowledge and alters behaviors surrounding financial management. Interest from academic and professional entities across the United States reflects recognition of the program as an emerging best practice. We describe lessons learned through program implementation, including demands for FES services throughout the academic year, and topics relevant to each student cohort. We propose that providing one-on-one financial advice to DVM students is a critical component of a broader financial education program. Actualizing timing, relevance, and individualization, this integrated approach optimizes opportunities for knowledge application and ultimately behavioral change.

Neuroprotection by post-stroke administration of an oral formulation of angiotensin-(1-7) in ischaemic stroke.

NEW FINDINGS: What is the central question of this study? Angiotensin-(1-7) decreases cerebral infarct volume and improves neurological function when delivered centrally before and during ischaemic stroke. Here, we assessed the neuroprotective effects of angiotensin-(1-7) when delivered orally post-stroke. What is the main finding and its importance? We show that oral delivery of angiotensin-(1-7) attenuates cerebral damage induced by middle cerebral artery occlusion in rats, without affecting blood pressure or cerebral blood flow. Importantly, these treatments begin post-stroke at times coincident with the treatment window for tissue plasminogen activator, providing supporting evidence for clinical translation of this new therapeutic strategy. ABSTRACT: As a target for stroke therapies, the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas [ACE2/Ang-(1-7)/Mas] axis of the renin-angiotensin system can be activated chronically to induce neuroprotective effects, in opposition to the deleterious effects of angiotensin II via its type 1 receptor. However, more clinically relevant treatment protocols with Ang-(1-7) that involve its systemic administration beginning after the onset of ischaemia have not been tested. In this study, we tested systemic post-stroke treatments using a molecule where Ang-(1-7) is included within hydroxypropyl-ß-cyclodextrin [HPßCD-Ang-(1-7)] as an orally bioavailable treatment. In three separate protocols, HPßCD-Ang-(1-7) was administered orally to Sprague-Dawley rats after induction of ischaemic stroke by endothelin-1-induced middle cerebral artery occlusion: (i) to assess its effects on cerebral damage and behavioural deficits; (ii) to determine its effects on cardiovascular parameters; and (iii) to determine whether it altered cerebral blood flow. The results indicate that post-stroke oral administration of HPßCD-Ang-(1-7) resulted in 25% reductions in cerebral infarct volumes and improvement in neurological functions (P < 0.05), without inducing any alterations in blood pressure, heart rate or cerebral blood flow. In conclusion, Ang-(1-7) treatment using an oral formulation after the onset of ischaemia induces significant neuroprotection in stroke and might represent a viable approach for taking advantage of the protective ACE2/Ang-(1-7)/Mas axis in this disease.

Local Delivery Is Critical for Monocyte Chemotactic Protein-1 Mediated Site-Specific Murine Aneurysm Healing.

BACKGROUND: Local delivery of monocyte chemotactic protein-1 (MCP-1/CCL2) via our drug-eluting coil has been shown to promote intrasaccular aneurysm healing via an inflammatory pathway. OBJECTIVE: In this study, we validate the importance of local MCP-1 in murine aneurysm healing. Whether systemic, rather than local, delivery of MCP-1 can direct site-specific aneurysm healing has significant translational implications. If systemic MCP-1 is effective, then MCP-1 could be administered as a pill rather than by endovascular procedure. Furthermore, we confirm that MCP-1 is the primary effector in our MCP-1 eluting coil-mediated murine aneurysm healing model. METHODS: We compare aneurysm healing with repeated intraperitoneal MCP-1 versus vehicle injection, in animals with control poly(lactic-co-glycolic) acid (PLGA)-coated coils. We demonstrate elimination of the MCP-1-associated tissue-healing response by knockout of MCP-1 or CCR2 (MCP-1 receptor) and by selectively inhibiting MCP-1 or CCR2. Using immunofluorescent probing, we explore the cell populations found in healed aneurysm tissue following each intervention. RESULTS: Systemically administered MCP-1 with PLGA coil control does not produce comparable aneurysm healing, as seen with MCP-1 eluting coils. MCP-1-directed aneurysm healing is eliminated by selective inhibition of MCP-1 or CCR2 and in MCP-1-deficient or CCR2-deficient mice. No difference was detected in M2 macrophage and myofibroblast/smooth muscle cell staining with systemic MCP-1 versus vehicle in aneurysm wall, but a significant increase in these cell types was observed with MCP-1 eluting coil implant and attenuated by MCP-1/CCR2 blockade or deficiency. CONCLUSION: We show that systemic MCP-1 concurrent with PLGA-coated platinum coil implant is not sufficient to produce site-specific aneurysm healing. MCP-1 is a critical, not merely complementary, actor in the aneurysm healing pathway.

Protective effects of the angiotensin II AT2 receptor agonist compound 21 in ischemic stroke: a nose-to-brain delivery approach.

Significant neuroprotective effects of angiotensin II type 2 (AT2) receptor (AT2 receptor) agonists in ischemic stroke have been previously demonstrated in multiple studies. However, the routes of agonist application used in these pre-clinical studies, direct intracerebroventricular (ICV) and systemic administration, are unsuitable for translation into humans; in the latter case because AT2 receptor agonists are blood-brain barrier (BBB) impermeable. To circumvent this problem, in the current study we utilized the nose-to-brain (N2B) route of administration to bypass the BBB and deliver the selective AT2 receptor agonist Compound 21 (C21) to naïve rats or rats that had undergone endothelin 1 (ET-1)-induced ischemic stroke. The results obtained from the present study indicated that C21 applied N2B entered the cerebral cortex and striatum within 30 min in amounts that are therapeutically relevant (8.4-9 nM), regardless of whether BBB was intact or disintegrated. C21 was first applied N2B at 1.5 h after stroke indeed provided neuroprotection, as evidenced by a highly significant, 57% reduction in cerebral infarct size and significant improvements in Bederson and Garcia neurological scores. N2B-administered C21 did not affect blood pressure or heart rate. Thus, these data provide proof-of-principle for the idea that N2B application of an AT2 receptor agonist can exert neuroprotective actions when administered following ischemic stroke. Since N2B delivery of other agents has been shown to be effective in certain human central nervous system diseases, the N2B application of AT2 receptor agonists may become a viable mode of delivering these neuroprotective agents for human ischemic stroke patients.

Post-stroke angiotensin II type 2 receptor activation provides long-term neuroprotection in aged rats.

Activation of the angiotensin II type 2 receptor (AT2R) by administration of Compound 21 (C21), a selective AT2R agonist, induces neuroprotection in models of ischemic stroke in young adult animals. The mechanisms of this neuroprotective action are varied, and may include direct and indirect effects of AT2R activation. Our objectives were to assess the long-term protective effects of post-stroke C21 treatments in a clinically-relevant model of stroke in aged rats and to characterize the cellular localization of AT2Rs in the mouse brain of transgenic reporter mice following stroke. Intraperitoneal injections of C21 (0.03mg/kg) after ischemic stroke induced by transient monofilament middle cerebral artery occlusion resulted in protective effects that were sustained for up to at least 3-weeks post-stroke. These included improved neurological function across multiple assessments and a significant reduction in infarct volume as assessed by magnetic resonance imaging. We also found AT2R expression to be on neurons, not astrocytes or microglia, in normal female and male mouse brains. Stroke did not induce altered cellular localization of AT2R when assessed at 7 and 14 days post-stroke. These findings demonstrate that the neuroprotection previously characterized only during earlier time points using stroke models in young animals is sustained long-term in aged rats, implying even greater clinical relevance for the study of AT2R agonists for the acute treatment of ischemic stroke in human disease. Further, it appears that this sustained neuroprotection is likely due to a mix of both direct and indirect effects stemming from selective activation of AT2Rs on neurons or other cells besides astrocytes and microglia.

Collision Cross Sections for 20 Protonated Amino Acids: Fourier Transform Ion Cyclotron Resonance and Ion Mobility Results.

We report relative dephasing cross sections for the 20 biogenic protonated amino acids measured using the cross sectional areas by Fourier transform ion cyclotron resonance (CRAFTI) technique at 1.9 keV in the laboratory reference frame, as well as momentum transfer cross sections for the same ions computed from Boltzmann-weighted structures determined using molecular mechanics. Cross sections generally increase with increasing molecular weight. Cross sections for aliphatic and aromatic protonated amino acids are larger than the average trend, suggesting these side chains do not fold efficiently. Sulfur-containing protonated amino acids have smaller than average cross sections, reflecting the mass of the S atom. Protonated amino acids that can internally hydrogen-bond have smaller than average cross sections, reflecting more extensive folding. The CRAFTI measurements correlate well with results from drift ion mobility (IMS) and traveling wave ion mobility (TWIMS) spectrometric measurements; CRAFTI results correlate with IMS values approximately as well as IMS and TWIMS values from independent measurements correlate with each other. Both CRAFTI and IMS results correlate well with the computed momentum transfer cross sections, suggesting both techniques provide accurate molecular structural information. Absolute values obtained using the various methods differ significantly; in the case of CRAFTI, this may be due to errors in measurements of collision gas pressure, measurement of excitation voltage, and/or dependence of cross sections on kinetic energy. Graphical Abstract ᅟ.

Linewidth pressure measurement: a new technique for high vacuum characterization.

Pressure measurement is often the limiting factor in the accuracy of quantitative ion-molecule experiments. We present a new method for pressure measurement based on analysis of pressure-limited Fourier transform ion cyclotron resonance (FTICR) linewidths for well-characterized collisions of Ar(+) with Ar. The kinetic energy dependence of Ar(+)/Ar collision cross sections is well-described using a single-parameter fitting procedure, which results in pressure measurements in good agreement with those from a cold cathode tube and from measurement of total ion signal following electron impact ionization. The new method avoids problems inherent in ionization-based methods, such as those arising from differences in ionization potential or perturbations to the pressure that occur during electron ionization of the gas to be measured, and should be applicable in the trapping cells of FTICR and Orbitrap mass spectrometers.

Visualizing flow trajectories using locality-based rendering and warped curve plots.

In flow simulations the behavior and properties of particle trajectories often depend on the physical geometry contained in the simulated environment. Understanding the flow in and around the geometry itself is an important part of analyzing the data. Previous work has often utilized focus+context rendering techniques, with an emphasis on showing trajectories while simplifying or illustratively rendering the physical areas. Our research instead emphasizes the local relationship between particle paths and geometry by using a projected multi-field visualization technique. The correlation between a particle path and its surrounding area is calculated on-the-fly and displayed in a non-intrusive manner. In addition, we support visual exploration and comparative analysis through the use of linked information visualization, such as manipulatable curve plots and one-on-one similarity plots. Our technique is demonstrated on particle trajectories from a groundwater simulation and a computer room airflow simulation, where the flow of particles is highly influenced by the dense geometry.

Combining local- and large-scale models to predict the distributions of invasive plant species.

Habitat distribution models are increasingly used to predict the potential distributions of invasive species and to inform monitoring. However, these models assume that species are in equilibrium with the environment, which is clearly not true for most invasive species. Although this assumption is frequently acknowledged, solutions have not been adequately addressed. There are several potential methods for improving habitat distribution models. Models that require only presence data may be more effective for invasive species, but this assumption has rarely been tested. In addition, combining modeling types to form "ensemble" models may improve the accuracy of predictions. However, even with these improvements, models developed for recently invaded areas are greatly influenced by the current distributions of species and thus reflect near- rather than long-term potential for invasion. Larger scale models from species' native and invaded ranges may better reflect long-term invasion potential, but they lack finer scale resolution. We compared logistic regression (which uses presence/absence data) and two presence-only methods for modeling the potential distributions of three invasive plant species on the Olympic Peninsula in Washington, USA. We then combined the three methods to create ensemble models. We also developed climate envelope models for the same species based on larger scale distributions and combined models from multiple scales to create an index of near- and long-term invasion risk to inform monitoring in Olympic National Park (ONP). Neither presence-only nor ensemble models were more accurate than logistic regression for any of the species. Larger scale models predicted much greater areas at risk of invasion. Our index of near- and long-term invasion risk indicates that < 4% of ONP is at high near-term risk of invasion while 67-99% of the Park is at moderate or high long-term risk of invasion. We demonstrate how modeling results can be used to guide the design of monitoring protocols and monitoring results can in turn be used to refine models. We propose that, by using models from multiple scales to predict invasion risk and by explicitly linking model development to monitoring, it may be possible to overcome some of the limitations of habitat distribution models.

Stimulation of mitochondrial biogenesis and autophagy by lipopolysaccharide in the neonatal rat cardiomyocyte protects against programmed cell death.

Adult rat cardiomyocytes in culture respond to sub-lethal doses of lipopolysaccharides (LPS) by activation of pathways including the production of TNF-alpha and increased apoptosis. We and others have demonstrated a protective phenotype for neonatal rat cardiomyocytes to LPS. Concentrations of LPS far exceeding those necessary to induce TNF-alpha release do not induce apoptosis in the neonatal cells, although these cells are fully capable or inducing apoptosis in response to multiple other stimuli. In neonatal cells, we demonstrate that LPS treatment leads to a loss of mitochondrial membrane potential (Deltapsi) which is temporally associated with an increase in the level of uncoupling protein 3 (UCP3). Cells remain viable with no measurable increase in apoptotic or necrotic cell death. Many markers of mitochondrial biogenesis are also activated. LPS treatment stimulates an increase in the (i) transcription of mitochondrial transcription factor A (Tfam), (ii) nuclear accumulation of redox-sensitive nuclear respiratory factor 1 (NRF-1), and (iii) expression of peroxisome proliferator-activated receptor gamma co-activator 1 (PGC-1). We also observed that LPS increased intracellular autophagy. Autophagy was assessed by monitoring the levels of a mammalian protein specifically associated with autophagosomes, microtubule-associated light chain 3 (LC3). Furthermore, inhibition of autophagy in the presence of LPS stimulates markers of apoptosis. Our data suggest that the protective response of neonatal cells to LPS is multi-faceted at the level of the mitochondrion. Viable cells replace dysfunctional mitochondria by mitochondrial biogenesis and the extent of the damage limited by the rapid removal of damaged organelles by the stimulation of autophagy.

A multi-level cache model for run-time optimization of remote visualization.

Remote visualization is an enabling technology aiming to resolve the barrier of physical distance. While many researchers have developed innovative algorithms for remote visualization, previous work has focused little on systematically investigating optimal configurations of remote visualization architectures. In this paper, we study caching and prefetching, an important aspect of such architecture design, in order to optimize the fetch time in a remote visualization system. Unlike a processor cache or web cache, caching for remote visualization is unique and complex. Through actual experimentation and numerical simulation, we have discovered ways to systematically evaluate and search for optimal configurations of remote visualization caches under various scenarios, such as different network speeds, sizes of data for user requests, prefetch schemes, cache depletion schemes, etc. We have also designed a practical infrastructure software to adaptively optimize the caching architecture of general remote visualization systems, when a different application is started or the network condition varies. The lower bound of achievable latency discovered with our approach can aid the design of remote visualization algorithms and the selection of suitable network layouts for a remote visualization system.

The response of neonatal rat ventricular myocytes to lipopolysaccharide-induced stress.

Sepsis induced by exposure to lipopolysaccharide (LPS) can be life-threatening and lead to multiple-organ dysfunction. Sepsis-associated cardiac dysfunction is a primary cause of mortality. The response of isolated cardiac myocytes to LPS exposure is poorly understood. Cultured neonatal rat ventricular cardiomyocytes were used to evaluate the response to LPS exposure. Other authors have reported that LPS exposure at doses sufficient to induce tumor necrosis factor alpha (TNF-alpha) production and apoptosis in adult cardiomyocytes do not induce apoptosis in neonatal cardiomyocytes. We therefore hypothesized that neonatal cardiomyocytes have innate protective mechanisms that protect from septic damage. Cultured neonatal rat ventricular cardiomyocytes were stimulated by exposure to LPS for varying lengths of time. NFkappaB signaling pathways, TNF-alpha production, and Akt activation were monitored. We also assessed the induction of apoptosis in these cells by monitoring caspase-3 activity. LPS rapidly stimulates nuclear translocation of NFkappaB and Akt activation. TNF-alpha production is also stimulated. However, high doses of LPS are unable to induce apoptosis in these cells, and protection is not a function of Akt activation. LPS treatment also stimulated the levels of cyclooxygenase-2 and the production of downstream metabolites, specifically PGE2 and 15deoxyDelta12-14PGJ2 (15dPGJ2). Specific inhibition of cyclooxygenase-2 activity induced apoptosis in the presence of LPS, whereas direct exposure to 15dPGJ2 at pharmacological levels induced apoptosis. Neonatal rat ventricular cardiomyocytes have innate protective mechanisms that prevent apoptotic cell death after LPS exposure. Metabolic products of arachidonic acid metabolized by the cyclooxygenase pathway can be potentially apoptotic or antiapoptotic. The balance of these products within these cells may define the cellular response to LPS exposure.

Fluorescence imaging microscopy of cellular markers in ischemic vs non-ischemic cardiomyopathy after left ventricular unloading.

BACKGROUND: The heart undergoes repair and initiates protective mechanisms via ventricular unloading. We examined the presence of 2 markers in pre-unloaded and post-unloaded human cardiac tissue that are important indicators of cardiac failure, tumor necrosis factor-alpha and inducible nitric oxide synthase. We also measured 2 nuclear transcription factors, NFkappaB50 and NFkappaB65, comparing quantities and localizations to determine if mechanical unloading reduced their presence, as these markers are also thought to be indicators of impending heart failure. Amounts and localizations in patients that had been diagnosed with either ischemic or non-ischemic cardiomyopathy were compared after mechanical unloading with a left ventricular assist device. To establish that unloading had been achieved, levels of atrial natriuretic protein were determined. METHODS: Core biopsies were harvested at assist device implantation and removal. Fluorescence deconvolution microscopy image reconstructions of fluorescence probes were correlated with data obtained by western Blot and electrobility shift assays. RESULTS: Statistically significant differences in localization and amounts of tumor necrosis factor and nitric oxide synthase were seen between pre- and post-assist device samples. Amounts of tumor necrosis factor and nitric oxide synthase in ischemic tissue were increased at the time of assist device removal, but decreased in dilated or idiomyopathic samples. Ventricular unloading resulted in reduced levels of natriuretic protein, with the greatest reduction being seen in ischemic tissue. Both NFkappaB50 and NFkappaB65 increased in ischemic tissue, but only NFkappaB50 in non-ischemic samples. CONCLUSIONS: Changes in localization of the factors and altered levels of cytokine and nitric oxide synthase indicate that the heart switches to a "protective and repair" mode, and mechanical unloading allows this transition to occur. Observed changes were dependent on the etiology of the disease.

Attenuation of fatty acid-induced apoptosis by low-dose alcohol in neonatal rat cardiomyocytes.

Moderate alcohol consumption has been shown to reduce the morbidity and mortality from coronary heart disease. Ethanol elicits its protective effects via mechanisms that include activation of protein kinases linked to growth and survival. Our results in isolated neonatal rat cardiomyocytes demonstrate that repeated short-term, low-dose exposure to ethanol is sufficient to activate the growth and/or survival pathways that involve PKC-epsilon, Akt, and AMP-activated kinase. In addition, we are able to induce apoptosis in these cardiomyocytes using the saturated fatty acid palmitate. Pretreatment with multiple low-dose ethanol exposures attenuates the apoptotic response to palmitate. This protection is manifested by a reduction in caspase-3-like activity, decreased mitochondrial loss of cytochrome c, and decreased loss of the mitochondrial lipid cardiolipin. We previously reported that incubation of cardiomyocytes with palmitate results in decreased production of reactive oxygen species compared with cells incubated with the nonapoptotic fatty acid oleate. In the present study, we observed an increase in the production of superoxide and the rates of fatty acid oxidation in cardiomyocytes pretreated with ethanol and then exposed to fatty acids. The level of superoxide production in palmitate-treated cells returns to the levels observed in oleate-treated cells after ethanol exposure. Taken together with our observed increase in AMP-activated kinase activity, we propose that ethanol pretreatments stimulate oxidative metabolism and electron transport within cardiomyocytes. We postulate that stimulation of palmitate metabolism may protect cardiomyocytes by preventing accumulation of unsaturated precursor molecules of cardiolipin synthesis. Maintaining cardiolipin levels may be sufficient to prevent the mitochondrial loss of cytochrome c and the downstream activation of caspases.